(CCSP073) MUSCLE SYMPATHETIC EXCITATORY RESPONSES TO DYNAMIC ONE-LEG CYCLING EXERCISE ARE AUGMENTED IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

Background: In patients with heart failure with reduced ejection fraction (HFrEF), the magnitude of sympathetic activation and exercise intolerance determines both quality of life and survival. We recently identified a ‘paradoxical’ reflex increase in muscle sympathetic nerve activity (MSNA) during one-leg dynamic cycling exercise in patients with HFrEF, which related inversely to exercise capacity. Our present aim was to test the hypothesis that patients with HF with preserved ejection fraction (HFpEF) also exhibit sympathoexcitation during dynamic exercise.

METHODS AND RESULTS: In 8 HFpEF patients (4 females; 70±7 yrs; LVEF: 64±5%; BNP: 340 pg/ml (121, 856) [median (IQR)]), 12 co-morbid controls (CMC; 4 females; 65±9 yrs; LVEF: 64±8%), matched for age, sex, medication, and presence of co-morbidities, including hypertension, obesity, diabetes, and sleep apnea, and 15 healthy controls (HC; 7 females; 64±9 yrs; LVEF: 66±5%), we measured, in the seated position, heart rate (HR), blood pressure (BP), and MSNA (microneurography) during 2 minutes of baseline, 4 minutes of one-leg cycling exercise (2 minutes each at mild and moderate intensity), and 2 minutes of recovery. Exercise capacity (peak oxygen uptake; V̇O2peak) was determined by open circuit spirometry. Resting HR and BP did not differ between groups (all P>0.05), whereas resting MSNA burst frequency was elevated in HFpEF (52±15 bursts/min) compared to both CMC (40±7 bursts/min; P=0.04) and HC (34±10 bursts/min; P< 0.01). In HFpEF, relative V̇O2peak (15±3 ml/kg/min) was lower compared to both CMC (26±7 ml/kg/min; P=0.01) and HC (31±9 ml/kg/min; P< 0.0001). During exercise, both HR (P < 0.001) and BP (P < 0.001) were increased with no differences between groups (all P>0.05). Compared to baseline, MSNA burst frequency was unchanged during mild (−4±5 bursts/min; P=0.13) and decreased during moderate (−7±9 bursts/min; P< 0.01) cycling exercise in HC, was unchanged during both mild (+3±7 bursts/min; P=0.26) and moderate (+3±8 bursts/min; P=0.19) cycling exercise in CMC, yet increased in patients with HFpEF during both mild (+14±8 bursts/min; P< 0.001) and moderate (+15±7 bursts/min; P< 0.001) cycling exercise. In the cohort as a whole, relative V̇O2peak related inversely to levels of MSNA burst frequency at rest (R2=0.32; P< 0.001) and during moderate exercise (R2=0.48; P< 0.0001).

Conclusion: Similar to HFrEF, patients with HFpEF also exhibit ‘paradoxical’ reflex sympathoexcitation during dynamic cycling exercise, unlike those with the co-morbidities that are common in this population. Furthermore, exercise capacity related inversely to MSNA during exercise, concordant with the concept of a neurogenic, vasoconstrictor limit on exercise in all with HF, regardless of phenotype.